Cetirizine is a metabolite of the anti-histamine, hydroxyzine. Similar to other second-generation anti-H1 receptor antagonists, cetirizine does not cross the blood brain barrier and is considered a peripherally active anti-histamine with few central nervous system effects. Studies have shown that cetirizine provides safe and effective, symptomatic relief of seasonal allergies. Advantages to using cetirizine as an anti-histamine include minimal sedative effect, little anticholinergic activity and a longer acting duration.
Cetirizine is water soluble, and rapidly absorbed. Tablets and syrup formulations of cetirizine have been commercially manufactured and marketed. However, cetirizine pharmaceutical formulations are subject to degradation that occurs during manufacture and storage. U.S. Pat. No. 6,171,618 teaches that an esterfication process of the cetirizine occurs when low molecular weight esters or alcohols are present in a reactive mixture with cetirizine. In particular, high boiling point alcohols, especially glycerin, should not be present during the manufacturing and in formulations of cetirizine. The resultant ester impurities can cause the formulations to deviate from regulatory purity requirements and decrease the shelf-life of the formulations.
Spill resistant pharmaceutical formulations have been described in U.S. Pat. Nos. 6,102,254, 6,071,523 and 6,399,079. The spill resistant formulations have been described by the physical properties of (a) extrudability under light manual pressure from a squeezable container or a proxy (e.g. a syringe with a 5 mm orifice), and (b) spreadability in a spoon bowl measured by extruding the formulation into a spoon bowl and determining whether the material levels or spreads to the edges of the spoon bowl Spreadability also contributes to accuracy of measurement.
Surprisingly, we have discovered a spill resistant cetirizine formulation, containing high levels of low molecular weight polyhydric alcohol that does not form the most common cetirizine formulation degradative products, has a high degree of purity and increased storage time.